Endothelial Progenitor Cell-Derived Factors Exert Neuroprotection in Cultured Cortical Neuronal Progenitor Cells

Abstract

There is substantial evidence that stem and progenitor cells secrete trophic factors that have potential for repairing injured tissues. We have previously reported that the conditioned medium (CM) obtained from endothelial progenitor cells (EPC) cultures protects striatal neurons against 3-nitropropionic acid-induced toxicity. In the present study we tested the hypothesis that EPC-CM may support cortical neuronal cell function and/or survival. EPC were isolated from the peripheral blood of healthy human donors and cultured in hypoxic conditions (1.5% O2) to stimulate the secretion of growth factors. The supernatant or conditioned medium (EPC-CM) was then collected and used for the various experiments. Primary cultures of cerebral cortex from fetal rat embryonic day 14 were treated with EPC-CM and challenged by glucose and serum deprivation. We observed that EPC-CM treatment significantly increased total cell number and cell viability in the cultures. Similarly, the number of lba1-expressing cells was significantly upregulated by EPC-CM, while western blot analyses for the astroglial marker glial fibrillary acidic protein did not show a marked difference. Importantly, the number of beta-lll-tubulin-positive neurons in the cultures was significantly augmented after EPC-CM treatment. Similarly, western blot analyses for beta-III-tubulin showed significant higher signal intensities. Furthermore, EPC-CM administration protected neurons against glucose- and serum deprivation-induced cell loss. In sum, our findings identified EPC-CM as a means to promote viability and/or differentiation of cortical neurons and suggest that EPC-CM might be useful for neurorestorative approaches.

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke

“…Similar to the beneficial effects observed after ischemic stroke, EPC-derived factors have been shown to protect cultured cortical neuronal progenitor cells from a metabolic injury induced by glucose and serum deprivation (Santo et al, 2020). Again, transplantation of EPCs to a mice model of traumatic brain injury led to elevations in neovasculogenesis and neurological recovery.…”

Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals

“…However, they can differentiate into monocytic cells that exhibit some endothelial markers and exert pro-angiogenic effects in vivo through a paracrine mechanism [ 41 , 42 ]. These CEPCs, also termed circulating angiogenic cells (CACs) or EC colony-forming units (EC-CFUs) [ 39 , 43 , 44 ], have the ability to secrete a variety of cytokines, growth factors, lipids, and extracellular matrix proteins, providing nutritional and anti-apoptotic support for a variety of other cells with regenerative potential (e.g., ECs, cardiomyocytes, mesenchymal stem cells (MSCs), and neural stem cells (NSCs)) [ 36 , 38 , 45 , 46 ]. This paracrine production includes the secretion of cytokines, growth factors, and chemokines (including VEGF, SDF-1, platelet-derived growth factor (PDGF), and G-CSF) that promote angiogenesis and endothelial proliferation and migration [ 46 , 47 , 48 ].…”